The long term purpose of this research is to characterize and investigate the function of the nervus terminalis, in mammals, as an intermediary in the relay of chemical signals from the external environment to the neuroendocrine cells of the brain and to determine if it acts alone or in concert with the olfactory, vomeronasal and/or trigeminal nerves. The nervus terminalis is the only cranial nerve which projects directly from the nose to the septal and preoptic areas of the forebrain, regions which have been implicated in the reception and coordination of stimuli that evoke specific behavioral and hormonal changes relevant to reproductive function. It is the least studied of the "olfactory" systems because of difficulty in distinguishing it from the olfactory and vomeronasal nerves. The finding of immunoreactive luteining hormone releasing hormone (LHRH) in nerves and ganglion cells associated with this nerve made anatomical distinction feasible and provided a tool for investigating the function of this nerve. The specific objectives of this investigation are: I. Characterization of the nervus terminalis in relation to the olfactory and vomeronasal nerves. Retrograde tracing and immunocytochemical techniques will be used to determine the extent of the central and peripheral projections of this nerve, if the projections are afferent and/or efferent, and identify the neurochemical substances present in the cells of origin of these projections. Steroid autoradiography will be used to examine possible receptor content of the cells in the nervus terminalis. II. Ultrastructural characterization of the nervus terminalis. Pre- embedding immunocytochemical staining procedures and electron microscopy will be used to examine the types of synapses found in the ganglia of this nerve and the types of endings made by the LHRH neurons in vomeronasal and olfactory epithelia, nasal blood vessels, and glands. III. Study of the ontogenesis of the LHRH cells and initial detection of LHRH mRNA in the nervus terminalis. Tritiated thymidine autoradiography and LHRH immunocytochemistry will be used to determine the time and site of origin (forebrain and/or olfactory placode) of the LHRH cells of the nervus terminalis. In situ hybridization with radiolabeled probes will be used to detect the presence of LHRH mRNA in the nervus terminalis, since this nerve appears to be the initial and principal source of the decapeptide in the fetus.